During the coming year we propose to continue our studies on the phenomena of surface digestion and membrane transport of folic acid polyglutamates. Existing evidence suggests that these are important events in the intestinal absorption of folate. We now wish to extend these observations to determine if they are important in the uptake of folate by isolated intestinal cells and lymphocytes. These studies should be facilitated by use of a semi-purified conjugase inhibitor currently available from red-kidney beans. We plan to continue efforts to isolate this inhibitor in pure form, as well as a supply of conjugase. In view of reports that conjugase levels are related to methotrexate resistance in bacteria, we propose to study the concentration of this enzyme in lymphocytes isolated from peripheral blood of patients undergoing methotrexate therapy for leukemia.